Genetics of Atrial Fibrillation


Atrial fibrillation (AF) is the most common sustained arrhythmia with poor prognosis, reaching epidemic proportions in the ageing population. The condition affects more than five million people worldwide and is a significant clinical problem. Of particular interest is a subset of younger patients (<60 years of age) who develop AF in the absence of known risk factors (such as advancing age, hypertension, structural heart disease and congestive heart failure), a condition classified as lone AF. Genetic variations in ion channel genes only account for a small percentage of the cases. Genome‐wide association studies (GWAS) look beyond the targeted genes and are capable of identifying novel mutations and genes, and biological pathways for AF. This review summarises the candidate gene and GWAS on AF, and discusses the application of exome sequencing approach in revisiting familial AF, as well as the potential clinical applications of the genetic data in the management of AF. A better understanding of the molecular mechanism of AF will aid the cardiologist in strategising the optimal therapeutic regimen for the patient.

Key Concepts:

  • Atrial fibrillation is an important clinical problem.

  • Atrial fibrillation is associated with genetic mutations in ion channel genes.

  • Genetic mutations often exhibit incomplete penetrance.

  • Genetic mutations may have functional impact on the ion channel.

  • Single‐nucleotide polymorphisms in ion channel genes only account for a small percentage of the cases.

  • The technology for identifying genetic variations is advancing rapidly.

  • Next‐generation sequencing is expected to become increasingly feasible.

  • The genetic data garnered from candidate gene and genome‐wide association studies have important clinical implications in management and treatment strategies of atrial fibrillation.

Keywords: atrial fibrillation; arrhythmias; genetic biomarkers; ion channels; genome‐wide association studies; candidate gene sequencing; exome sequencing

Figure 1.

Schematic diagram illustrating the diverse genetic causes of atrial fibrillation.



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Koo, Seok Hwee, Ku, Chee Seng, Chen, Lin Yee, and Lee, Edmund Jon Deoon(Nov 2011) Genetics of Atrial Fibrillation. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0023215]